This application (M738) describes the titration method to determine the water content of lyophilized pharmaceutical products by automated coulometric titration using a Karl Fischer titrator and an InMotion™ autosampler.
By downloading this application package, you will receive a PDF of the application note as well as the required data for the LabX™ titration software method.
In this (M762) application, an automated coulometric titration method using a Karl Fischer titrator and InMotion™ autosampler is described to determine the water content of lyophilized pharmaceutical products. The LabX balance provides the actual sample weight as part of the method.
By downloading this application package, you will receive a PDF of the application note as well as the required data for the LabX™ titration software method.
What is lyophilization?
Lyophilization is a dehydration process typically used to preserve material by freezing the material. The reduced surrounding pressure allows the frozen solvent to sublime directly from the solid phase to the gas phase. After this drying process, the final residual water content in the product is very low, around 1% to 4%.
Why perform lyophilization?
A significant proportion of active pharmaceutical ingredients are unstable in liquid formulations; thus, they need to be stored in the solid form. To achieve this, drugs are lyophilized to remove water from the formulations. This lyophilized powder is easier to transport and has an increased shelf life.
Role of Karl Fischer titration
The water content in lyophilized samples need to be below the permissible limit. Karl Fischer (KF) titration is commonly used to determine this. In a KF titration, the amount of water is calculated from the amount of iodine consumed to reach the endpoint of the following reaction.
CH3OH + SO2 + 3 RN + H2O + I2 → 2 [RNH]I + [RNH]SO4CH3
In coulometric KF titration, the iodine is generated by an electrochemical reaction in the cell. For more information on the basics, methods, and techniques of Karl Fischer titration, review our Karl Fischer Titration Guides.
Please note, this product is not intended for medical use.
